Driving Down COGS: Leveraging Automation Technologies And Mitigating Risk
By Life Science Connect Editorial Staff
As cell therapies continue to grow as a segment of the greater biopharmaceutical pipeline, the technologies supporting their manufacturing will likewise continue to evolve to enable better yields, higher production volumes, and improved consistency. This is particularly true for the technologies aimed at automating and standardizing cell therapy production, which are poised to offer organizations process-level improvements that streamline and accelerate workflows.
In a recent installment of Cell & Gene Live, Craig Beasley, chief technical officer at BlueRock Therapeutics, and Narinder Singh, chief technical officer at Arcellx, discussed the emerging technologies that can support automation for cell therapy manufacturing, as well as how their organizations and others can standardize and integrate process steps through automated solutions.
Technology Needs For Automated Manufacturing
When it comes to cell therapy manufacturing, certain steps, such as washing and expansion, are ripe for automation across the industry at large, according to Beasley. “Those types of solutions are a big win for all of us and allow us to focus on more detailed automation around transfection steps or differentiation steps that are very specific to a product,” he said. Combining more standard automation with bespoke solutions can offer companies compounding gains for their processes; understanding the most crucial points in a process and how automation might help support or improve those workflow steps is likewise key to maximizing the value of automation activities.
Data is a critical component in determining the reliability and reproducibility of automated technologies, Singh said, adding that some available automation does not have adequate data integration, requiring companies to vet suppliers and create solutions where necessary. “The other thing we’re focusing on is how to close processes and achieve material transfer and handling in a more reproducible way,” Singh said. Key to this reproducibility is minimizing contamination risk through at-line or online analytics, as well as enabling better cryopreservation, ideally at the point of collection for patient samples.
Ultimately, scalability is one of the biggest challenges facing cell therapy manufacturing. For autologous applications, this means focusing on driving down processing time in order to facilitate the production of as many lots as possible within a fixed overhead. To this end, there are two areas positioned for immediate improvement: controlling raw material inputs to limit variability and moving toward achieving allogeneic production for these modalities. “I think the way to really make it scalable is to move to allogeneic,” Beasley said. “I think the future of pluripotent stem cells and differentiating into the right target cells gets around a big bottleneck for the world. It’s not going to be ready overnight, but I think that will be the key to making this really scalable and making sure we’re not just treating patients in the U.S., EU, and Japan and Australia, but all around the world.”
Mitigating Risk In Process Automation
Scalability is important for more than just meeting market demand – done right, it can serve to minimize risk. Often, early development yields a process that is highly customized and reliant on academic laboratory strategies not designed to scale. “Turning these academic processes into industrial scale, high-throughput processes requires a holistic approach,” Singh said. The holy grail would be to define a construct for an allogeneic manufacturing process that meets the needs of an entire patient population and is poised to produce on demand. “There is a lot of work left for us, for process scientists and engineers, to work through all of these details.”
The industry is still far from realizing widespread allogeneic manufacturing, making de-risking autologous applications crucial for the near term. Much of this risk assessment centers on minimizing variability for the patient materials, reagents, and media that go into a process; other considerations, such as operator-to-operator variability and the contamination risks associated with open processing, can be more easily addressed through automation solutions. “I think closing systems and reducing manual manipulations is critical,” Beasley said. “Also, by automating the routine steps, you get to train people more closely on what is really critical.”
Automating the more repetitive unit operations in a workflow can also help improve consistency for the steps that still require manual manipulation. By allowing operators to focus on fewer steps requiring more expertise, programs can train more closely on more critical processes, as well as focus more on early intervention when processes deviate. This increased focus can, in turn, help inform technology improvements for suppliers, facilitating better automation and enabling its expansion into other unit operations as more basic ones achieve optimization.